人表皮生长因子受体2阴性晚期胃癌患者程序性死亡受体1抑制剂免疫治疗过程中癌胚抗原变化及对治疗效果的影响  

Changes of carcinoembryonic antigen in programmed death receptor 1 inhibitor immunotherapy in human epidermal growth factor receptor 2 negative advanced gastric cancer patients and its effect on therapeutic effect

作　　者：周弦 梅林 ZHOU Xian;MEI Lin(Department of Oncology,Anqing 116 Hospital,Anqing 246003,China)

机构地区：[1]安庆一一六医院肿瘤内科,安徽安庆246003

出　　处：《胃肠病学和肝病学杂志》2025年第3期350-357,共8页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的探讨人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阴性晚期胃癌患者接受程序性死亡受体1(programmed death-1,PD-1)抑制剂免疫治疗过程中癌胚抗原(carcinoembryonic antigen,CEA)变化及与预后的关系。方法选取2020年5月至2023年5月于我院住院治疗的HER2阴性的转移性胃癌或局部晚期胃癌患者80例为研究对象,入组患者均采用PD-1抑制剂联合化疗治疗。使用曲线估计对多次测量的CEA值构建线性模型Y=ax+b,a为斜率,b为常数。根据最大正确诊断指数对应的斜率(a=0.85),CEA变化趋势分为缓慢上升型(a≤0.85)58例,纳入缓慢组,快速上升型(a>0.85)22例,纳入快速组。比较PD-1抑制剂联合化疗治疗后,缓慢组和快速组的近期疗效、远期疗效以及不良反应。使用Kaplan-Meier法和Log-rank检验评价CEA变化趋势对总生存期(overall survival,OS)和无进展生存期(progression free survival,PFS)的影响。结果PD-1抑制剂联合化疗治疗过程中,不同测量时间的CEA水平呈双峰分布,整体呈上升趋势。与快速组相比,缓慢组的疾病稳定(stable disease,SD)病例占比较高,疾病进展(progression disease,PD)病例占比较低,差异有统计学意义(P<0.05)。在不良事件方面,与快速组相比,缓慢组≥3级不良事件发生率及总不良事件发生率均较低,缓慢组反应性毛细血管增生症(reactive capillary proliferation disease,RCCEP)发生率较低,差异有统计学意义(P<0.05)。在1~2级不良反应中,与快速组相比,缓慢组RCCEP发生率较低、ALT升高发生率较低,差异有统计学意义(P<0.05)。缓慢组与快速组中位PFS(median PFS,mPFS)分别为3.87个月和2.42个月,差异有统计学意义(P=0.024)。性别分层交互检验分析显示,性别不会影响CEA变化情况与患者mPFS的关系。Cox多因素回归分析结果显示,转移灶数目、CEA变化情况、腹膜转移、肝转移、评分、分化程度是HER2阴性晚期胃癌患者预后不良的独Objective To investigate the changes of carcinoembryonic antigen(CEA)levels during immunization with programmed death-1(PD-1)inhibitors in patients with advanced gastric cancer who are negative for human epidermal growth factor receptor 2(HER2),and to examine the relationship between these changes and patient prognosis.Methods We selected 80 patients with HER2-negative metastatic or locally advanced gastric cancer treated from May 2020 to May 2023.All patients received a combination of PD-1 inhibitors and chemotherapy.A linear model(Y=ax+b)was constructed for multiple CEA measurements,where(a)represents the slope and(b)the constant.Based on the optimal diagnostic index slope(a=0.85),we classified CEA change trends into two categories:a slow-rising type(a≤0.85)comprising 58 cases,termed the slow group,and a rapid-rising type(a>0.85)consisting of 22 cases,termed the rapid group.We compared short-term efficacy,long-term efficacy and adverse reactions between the two groups.The Kaplan-Meier method and Log-rank test were utilized to assess the impact of CEA change trends on overall survival(OS)and progression-free survival(PFS).Results During treatment with PD-1 inhibitors and chemotherapy,CEA levels exhibited a bimodal distribution across different measurement times,showing an overall upward trend.The slow group had a significantly higher number of stable disease(SD)cases and a lower incidence of disease progression(PD)compared to the rapid group.In terms of adverse events,the slow group reported a lower incidence of grade≥3 adverse events as well as a reduced total occurrence of adverse events,including reactive capillary hyperplasia(RCCEP).Among grade 1-2 adverse reactions,the rates of RCCEP and increased ALT levels in the slow group were significantly lower than those in the rapid group.The median PFS(mPFS)for the slow and rapid groups were 3.87 months and 2.42 months,respectively(P=0.024).Gender-stratified interaction tests indicated that gender did not influence the relationship between CEA changes and mPFS.

关 键 词：人表皮生长因子受体2阴性 胃癌 程序性死亡受体1抑制剂 化学治疗 癌胚抗原 

分 类 号：R735.2[医药卫生—肿瘤]